Circadian rhythmicity represents a complex behavioural and physiological phenotype. Clock genes have been identified in non-mammalian organisms, most notably, the period (per) and timeless (tim) genes in Drosophila and the frequency (frq) gene in Neurospora (reviewed in J. C. Hall, Trends Neurosci., 18: 230-240, 1995; J. C. Dunlap, Ann.Rev.Genet., 30: 579-601, 1996). A mouse clock gene has recently been identified by positional cloning (D. P. King et al., Cell, 89: 641-653, 1997). Mutation and transgenic studies (M. P. Antoch et al., Cell, 89: 655-667, 1997) confirm the involvement of the clock gene in circadian rhythmicity. The mouse clock protein contains both a DNA binding domain and a protein dimerisation domain indicating that it could, in combination with other proteins, regulate circadian rhythmicity by regulating gene transcription. The pattern of mouse clock gene expresssion is consistent with its role in circadian rhythms with highest levels of expression in the hypothalamus and eye, both of which are known to contain self-sustaining circadian oscillators. The mouse clock gene is also expressed in many tissues throughout the body. Similarly the drosophila gene has a wide tissue distribution pattern.
Recently Nagase, T. et al (DNA Res. 4, 141-150, 1997) published a set of full-length, but unidentified cDNAs expressed in human brain. The present invention identifies one of these cDNA sequences as encoding a human clock gene. The gene from which this human clock cDNA has been derived has been mapped to chromosome 4 (Nagase, T. et al (DNA Res. 4, 141-150, 1997). It has been predicted independently that the human clock gene maps to 4q12-4q13 by synteny with the mouse clock locus (King, D P et al Genetics 146, 1049-1060, 1997).